Trial Outcomes & Findings for A Study of Duloxetine in Elderly Generalized Anxiety Disorder (NCT NCT01118780)

NCT ID: NCT01118780

Last Updated: 2013-09-02

Results Overview

The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 291 participants
• Primary outcome timeframe: Baseline, Week 10
• Results posted on: 2013-09-02

Participant Flow

Study had 3 periods: a screening period (3 to 30 days prior to randomization, no study drug administered), a treatment period (10 weeks), and a taper period (2 weeks). Participants who completed the treatment period were considered to have completed the study. Participant Flow and results, unless specified otherwise, are during treatment period.

Participant milestones

Measure	Duloxetine 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Study STARTED	151	140
Overall Study COMPLETED	115	105
Overall Study NOT COMPLETED	36	35

Reasons for withdrawal

Measure	Duloxetine 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Study Adverse Event	15	15
Overall Study Death	1	0
Overall Study Lack of Efficacy	2	6
Overall Study Physician Decision	2	0
Overall Study Protocol Violation	3	6
Overall Study Withdrawal by Subject	13	8

Baseline Characteristics

A Study of Duloxetine in Elderly Generalized Anxiety Disorder

Baseline characteristics by cohort

Measure	Duloxetine n=151 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=140 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Total n=291 Participants Total of all reporting groups
Age Continuous	71.43 years STANDARD_DEVIATION 5.39 • n=5 Participants	71.70 years STANDARD_DEVIATION 5.04 • n=7 Participants	71.56 years STANDARD_DEVIATION 5.22 • n=5 Participants
Sex: Female, Male Female	114 Participants n=5 Participants	112 Participants n=7 Participants	226 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	28 Participants n=7 Participants	65 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	55 Participants n=5 Participants	47 Participants n=7 Participants	102 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	96 Participants n=5 Participants	93 Participants n=7 Participants	189 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	129 Participants n=5 Participants	120 Participants n=7 Participants	249 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Argentina	17 participants n=5 Participants	12 participants n=7 Participants	29 participants n=5 Participants
Region of Enrollment Austria	13 participants n=5 Participants	10 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment Canada	10 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Germany	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Mexico	21 participants n=5 Participants	21 participants n=7 Participants	42 participants n=5 Participants
Region of Enrollment Poland	27 participants n=5 Participants	29 participants n=7 Participants	56 participants n=5 Participants
Region of Enrollment Puerto Rico	7 participants n=5 Participants	5 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Spain	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment United Kingdom	10 participants n=5 Participants	7 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants	19 participants n=7 Participants	36 participants n=5 Participants
Hamilton Anxiety Rating Scale (HAMA) Total Score	24.62 units on a scale STANDARD_DEVIATION 6.40 • n=5 Participants	24.36 units on a scale STANDARD_DEVIATION 7.11 • n=7 Participants	24.49 units on a scale STANDARD_DEVIATION 6.74 • n=5 Participants
Years Since Onset of Generalized Anxiety Disorder (GAD)	12.78 years STANDARD_DEVIATION 16.40 • n=5 Participants	11.83 years STANDARD_DEVIATION 14.55 • n=7 Participants	12.32 years STANDARD_DEVIATION 15.52 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 10

Population: Randomized participants with a baseline and at least 1 post-baseline HAMA Total Score.

The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.

Outcome measures

Measure	Duloxetine n=143 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=131 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) Total Score	-15.86 units on a scale Standard Error 0.63	-11.69 units on a scale Standard Error 0.67	—

SECONDARY outcome

Timeframe: Baseline, Week 10

Population: Randomized participants with a baseline and at least 1 post-baseline SDS Global Functional Impairment Score.

The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Functional Impairment Score (SDS Global Score) was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.

Outcome measures

Measure	Duloxetine n=140 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=131 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Global Functional Impairment Score	-8.60 units on a scale Standard Error 0.60	-5.37 units on a scale Standard Error 0.64	—

SECONDARY outcome

Timeframe: Baseline, Week 10

Population: Randomized participants with a baseline and at least 1 post-baseline HAMA factor or item score.

The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Psychic Anxiety Factor Score was the sum of Items 1 to 6 and Item 14 and could have ranged from 0 to 28. The HAMA Somatic Anxiety Factor Score was the sum of Items 7 to 13 and could have ranged from 0 to 28. The HAMA Anxious Mood Item Score was the score for Item 1 and the HAMA Tension Item Score was the score for Item 2. In each case, higher scores indicated a greater degree of symptom severity. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.

Outcome measures

Measure	Duloxetine n=143 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=131 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) HAMA Psychic Anxiety Factor Score (n=143, 131)	-8.59 units on a scale Standard Error 0.36	-6.19 units on a scale Standard Error 0.38	—
Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) HAMA Somatic Anxiety Factor Score (n=143, 131)	-7.33 units on a scale Standard Error 0.33	-5.57 units on a scale Standard Error 0.35	—
Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) HAMA Anxious Mood Item Score (n=142, 131)	-1.77 units on a scale Standard Error 0.08	-1.24 units on a scale Standard Error 0.09	—
Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) HAMA Tension Item Score (n=143, 131)	-1.48 units on a scale Standard Error 0.08	-1.17 units on a scale Standard Error 0.09	—

SECONDARY outcome

Timeframe: Baseline, Week 10

Population: Randomized participants with a baseline and at least 1 post-baseline HADS Subscale Score.

HADS was a 14-item questionnaire with 2 subscales (anxiety and depression). Each item was rated on a 4-point scale (0 to 3) and higher scores indicated a greater dysfunction. The HADS Anxiety Subscale Score was the sum of the odd numbered items and scores could have ranged from 0 to 21. The HADS Depression Subscale Score was the sum of the even numbered items and scores could have ranged from 0 to 21. Higher scores indicated a greater dysfunction. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.

Outcome measures

Measure	Duloxetine n=143 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=132 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Change From Baseline to Week 10 Endpoint in Hospital Anxiety Depression Scale (HADS) Subscale Scores HADS Anxiety Subscale	-7.81 units on a scale Standard Error 0.37	-5.62 units on a scale Standard Error 0.39	—
Change From Baseline to Week 10 Endpoint in Hospital Anxiety Depression Scale (HADS) Subscale Scores HADS Depression Subscale	-3.29 units on a scale Standard Error 0.29	-1.61 units on a scale Standard Error 0.31	—

SECONDARY outcome

Timeframe: Week 10

Population: Randomized participants with at least 1 post-baseline CGI-Improvement Score.

CGI-Improvement measured the clinician's perception of the participant's improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much improved) to 7 (very much worse). Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit.

Outcome measures

Measure	Duloxetine n=143 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=132 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Clinical Global Impressions of Improvement Scale (CGI-Improvement) at Week 10	2.10 units on a scale Standard Error 0.10	2.63 units on a scale Standard Error 0.10	—

SECONDARY outcome

Timeframe: Week 10

Population: Randomized participants with at least 1 post-baseline PGI-Improvement Score.

PGI-Improvement measured the participant's perception of his or her improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much better) to 7 (very much worse). Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit.

Outcome measures

Measure	Duloxetine n=143 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=132 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Patient's Global Impressions of Improvement Scale (PGI-Improvement) at Week 10	2.35 units on a scale Standard Error 0.11	2.97 units on a scale Standard Error 0.12	—

SECONDARY outcome

Timeframe: Baseline, Week 10

Population: Randomized participants with a baseline and at least 1 post-baseline BPI-SF Pain Severity or Interference Subscale Score.

The BPI-SF Pain Severity Subscale was a participant-rated questionnaire that measured the severity of pain. Severity scores could have ranged from 0 (no pain) to 10 (pain as bad as you can imagine) for questions assessing worst pain, least pain, and average pain in the past 24 hours, and pain right now. The BPI-SF Interference Subscale measured the interference of pain with the participant's ability to function. Interference scores could have ranged from 0 (does not interfere) to 10 (completely interferes) for questions assessing interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Least squares (LS) means were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.

Outcome measures

Measure	Duloxetine n=141 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=132 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales Worst Pain (n=141, 132)	-1.44 units on a scale Standard Error 0.21	-0.90 units on a scale Standard Error 0.22	—
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales Least Pain (n=141, 132)	-0.92 units on a scale Standard Error 0.17	-0.50 units on a scale Standard Error 0.19	—
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales Average Pain (n=141, 132)	-1.10 units on a scale Standard Error 0.18	-0.68 units on a scale Standard Error 0.19	—
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales Pain Right Now (n=141, 132)	-0.81 units on a scale Standard Error 0.18	-0.59 units on a scale Standard Error 0.20	—
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales General Activity (n=140, 131)	-1.45 units on a scale Standard Error 0.23	-0.92 units on a scale Standard Error 0.24	—
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales Mood (n=140, 131)	-1.59 units on a scale Standard Error 0.22	-1.19 units on a scale Standard Error 0.23	—
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales Walking Ability (n=140, 131)	-0.91 units on a scale Standard Error 0.23	-0.31 units on a scale Standard Error 0.24	—
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales Normal Work (n=139, 131)	-1.21 units on a scale Standard Error 0.23	-0.83 units on a scale Standard Error 0.24	—
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales Relations With Other People (n=140, 131)	-0.96 units on a scale Standard Error 0.21	-0.80 units on a scale Standard Error 0.22	—
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales Sleep (n=140, 131)	-1.58 units on a scale Standard Error 0.27	-1.07 units on a scale Standard Error 0.28	—
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales Enjoyment of Life (n=140, 131)	-1.74 units on a scale Standard Error 0.23	-1.24 units on a scale Standard Error 0.24	—

SECONDARY outcome

Timeframe: Baseline, Week 10

Population: Randomized participants with a baseline and at least 1 post-baseline Q-LES-Q-SF Total Score; Last observation carried forward (LOCF).

The Q-LES-Q-SF was a participant-rated questionnaire designed to assess the degree of enjoyment and satisfaction experienced during the past week. The questionnaire consisted of 16 items rated on a 5-point scale ranging from 1 (very poor) to 5 (very good). The total raw score was the sum of Items 1 to 14 and could have ranged from 14 to 70. Total raw scores were converted to, and expressed as, the percentage of the maximum possible score. Percent=100*(total raw score - 14)/56. Higher scores indicated higher levels of enjoyment/satisfaction. Least squares (LS) mean were calculated and analyzed using analysis of covariance (ANCOVA) adjusted for treatment, pooled investigator, age category, and baseline.

Outcome measures

Measure	Duloxetine n=134 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=125 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Change From Baseline to Week 10 in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Total Score	15.11 percent of maximum possible score Standard Error 1.45	9.35 percent of maximum possible score Standard Error 1.52	—

SECONDARY outcome

Timeframe: Baseline through 10 weeks

Population: Randomized participants with a baseline and at least 1 post-baseline C-SSRS Score.

The C-SSRS captured the occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Suicidal behavior: a "yes" answer to any 1 of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Treatment-emergent was the worsening or new occurrence of suicidal behavior or ideation during treatment compared with baseline (Week 0).

Outcome measures

Measure	Duloxetine n=144 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=133 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Number of Participants With Treatment-Emergent Suicide-Related Ideation and Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS) Treatment-Emergent Suicidal Ideation	3 participants	5 participants	—
Number of Participants With Treatment-Emergent Suicide-Related Ideation and Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS) Treatment-Emergent Suicidal Behavior	0 participants	0 participants	—

SECONDARY outcome

Timeframe: Baseline, Week 10

Population: Randomized participants with a baseline and at least 1 post-baseline SDS Work/School, Social Life/Leisure Activities, or Family/Home Management Individual Impairment Scores.

The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). Higher values indicated a higher functional impairment in the participant's work/social/family life. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.

Outcome measures

Measure	Duloxetine n=140 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=131 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores Work/School (n=56, 51)	-2.21 units on a scale Standard Error 0.33	-1.08 units on a scale Standard Error 0.40	—
Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores Social Life/Leisure Activities (n=140, 131)	-2.84 units on a scale Standard Error 0.22	-1.94 units on a scale Standard Error 0.23	—
Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores Family/Home Management (n=140, 131)	-2.82 units on a scale Standard Error 0.22	-1.61 units on a scale Standard Error 0.24	—

SECONDARY outcome

Timeframe: Baseline, Week 10

Population: Randomized participants with a baseline and 1 post-baseline HAMA Total Score; Last observation carried forward (LOCF).

Response was a ≥50% improvement (reduction) in the Hamilton Anxiety Rating Scale (HAMA) Total Score at treatment period endpoint compared with baseline. Two definitions were used to determine remission: Definition 1 (HAMA Total Score ≤7 at endpoint) and Definition 2 (HAMA Total Score ≤10 at endpoint). The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.

Outcome measures

Measure	Duloxetine n=143 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=132 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates) Response	71.3 percentage of participants	45.5 percentage of participants	—
Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates) Remission (HAMA Total Score ≤7)	44.8 percentage of participants	29.5 percentage of participants	—
Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates) Remission (HAMA Total Score ≤10)	62.2 percentage of participants	40.2 percentage of participants	—

SECONDARY outcome

Timeframe: Week 10

Population: All randomized participants with at least 1 post-baseline SDS Global Score; Last observation carried forward (LOCF).

Two definitions, using the Sheehan Disability Scale (SDS) Global Functional Impairment Score (SDS Global Score), were used to determine functional remission: Definition 1 (SDS Global Score ≤5 at endpoint) and Definition 2 (SDS Global Score ≤6 at endpoint). The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Score was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life.

Outcome measures

Measure	Duloxetine n=151 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=140 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Percentage of Participants With Functional Remission at Week 10 (Functional Remission Rate) Functional Remission (SDS Global Score ≤6)	60.9 percentage of participants	40.7 percentage of participants	—
Percentage of Participants With Functional Remission at Week 10 (Functional Remission Rate) Functional Remission (SDS Global Score ≤5)	55.0 percentage of participants	32.9 percentage of participants	—

SECONDARY outcome

Timeframe: (Baseline through 10 weeks) and (Baseline, Week 2 through Week 10)

Population: Randomized participants who had baseline and the required number of post-baseline HAMA Total Scores.

Two definitions, using the Hamilton Anxiety Rating Scale (HAMA) Total Score at endpoint compared with baseline, were used to determine sustained improvement: Definition 1 [sustained improvement overall required a ≥30% improvement (reduction) in the HAMA Total Score at treatment period endpoint, at an earlier visit prior to endpoint, and at all visits in between] and Definition 2 (sustained improvement from Week 2 required a ≥30% reduction at treatment period endpoint, at Week 2, and at all visits in between). Both definitions required at least 2 post-baseline visits. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.

Outcome measures

Measure	Duloxetine n=134 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=124 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Percentage of Participants With Sustained Improvement (Sustained Improvement Rate) Sustained Improvement Overall (n=134, 124)	74.6 percentage of participants	55.6 percentage of participants	—
Percentage of Participants With Sustained Improvement (Sustained Improvement Rate) Sustained Improvement From Week 2 (n=134, 123)	26.9 percentage of participants	17.9 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline through 10 weeks

Population: All randomized participants.

The number of participants who discontinued from the study due to an AE (serious or other AE) during the treatment period. A summary of serious and other AEs is located in the Reported Adverse Events module.

Outcome measures

Measure	Duloxetine n=151 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=140 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Adverse Events (AEs) Leading to Discontinuation From Study	16 participants	15 participants	—

SECONDARY outcome

Timeframe: Baseline through 10 weeks

Population: Randomized participants with no falls recorded at Baseline and at least 1 post-baseline assessment for falls.

The percentage of participants who reported 1 or more falls at or before Week 10.

Outcome measures

Measure	Duloxetine n=113 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=114 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Percentage of Participants Reporting Falling Down	6.2 percentage of participants	3.5 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline through 10 weeks

Population: All randomized participants. The number of censored participants (n)=36 participants in the duloxetine treatment arm and n=60 participants in the placebo treatment arm.

The time (days) to first response, defined as a ≥50% improvement (reduction) from baseline in the Hamilton Anxiety Rating Scale (HAMA) Total Score. Participants who did not have a response were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.

Outcome measures

Measure	Duloxetine n=151 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=140 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Time to First Response	50.00 days Interval 48.0 to 51.0	70.00 days Interval 50.0 to 72.0	—

SECONDARY outcome

Timeframe: Baseline through 10 weeks

Population: All randomized participants (pts). The number of censored pts (n)=72 pts in the duloxetine treatment arm and n=92 pts in the placebo treatment arm for time to first remission (HAMA Total Score ≤7) and n=49 pts in the duloxetine treatment arm and n=71 pts in the placebo treatment arm for the time to first remission (HAMA Total Score ≤10).

The time (days) to first remission. Two definitions, using the Hamilton Anxiety Rating Scale (HAMA) Total Score, were used to determine remission: Definition 1 (HAMA Total Score ≤7 at endpoint) and Definition 2 (HAMA Total Score ≤10 at endpoint). Participants who did not have remission were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.

Outcome measures

Measure	Duloxetine n=151 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=140 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Time to First Remission Remission (HAMA Total Score ≤7)	71.00 days Interval 69.0 to 72.0	NA days Interval 72.0 to The median and upper confidence interval was not calculable because an insufficient number of participants reached the event (HAMA Total Score ≤7).	—
Time to First Remission Remission (HAMA Total Score ≤10)	51.00 days Interval 50.0 to 57.0	71.00 days Interval 70.0 to 75.0	—

SECONDARY outcome

Timeframe: Baseline through 10 weeks

Population: All randomized participants. The number of participants censored (n)=43 participants in the duloxetine treatment arm and n=63 participants in the placebo treatment arm.

Time (days) to the earliest visit at which the Hamilton Anxiety Rating Scale (HAMA) Total Score was a ≥30% improvement (reduction) from baseline that was sustained through the last treatment period visit. Participants who did not meet sustained improvement criteria were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.

Outcome measures

Measure	Duloxetine n=151 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=140 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Time to Sustained Improvement Overall	30.00 days Interval 29.0 to 48.0	50.00 days Interval 30.0 to The upper 95% confidence interval was not calculable due to an insufficient number of participants reaching the event by 10 weeks.	—

SECONDARY outcome

Timeframe: Baseline through 10 weeks

Population: All randomized participants (pts). Number of pts censored (n)=50 pts in duloxetine treatment arm and n=73 pts in placebo treatment arm for time to first functional remission (SDS Global Score ≤5) and n=37 pts in duloxetine treatment arm and n=60 pts in placebo treatment arm time to first functional remission (SDS Global Score ≤6).

Time (days) to first functional remission. Two definitions, using the Sheehan Disability Scale (SDS) Global Functional Impairment Score (SDS Global Score), were used to determine functional remission: Definition 1 (SDS Global Score ≤5 at endpoint) and Definition 2 (SDS Global Score ≤6 at endpoint). Participants, who did not have an SDS Global Score ≤5 or ≤6, were censored at the last treatment period visit. The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Score was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life.

Outcome measures

Measure	Duloxetine n=151 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=140 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Time to First Functional Remission Functional Remission (SDS Global Score ≤5)	50.00 days Interval 48.0 to 68.0	72.00 days Interval 71.0 to The upper 95% confidence interval was not calculable because an insufficient number of participants had functional remission (SDS Global Score ≤5) by endpoint.	—
Time to First Functional Remission Functional Remission (SDS Global Score ≤6)	31.00 days Interval 29.0 to 49.0	71.00 days Interval 50.0 to 73.0	—

SECONDARY outcome

Timeframe: Baseline through 10 weeks

Population: All randomized participants. The number of participants censored (n)=37 participants in the duloxetine treatment arm and n=58 participants in the placebo treatment arm.

The time (days) to first improvement, defined as a Clinical Global Impression of Improvement (CGI-Improvement) Score ≤2. Participants who did not have a CGI-I Score ≤2 were censored at the last treatment period visit. CGI-Improvement measured the clinician's perception of the participant's improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much improved) to 7 (very much worse). A CGI-Improvement Score of ≤2 was much improved or very much improved.

Outcome measures

Measure	Duloxetine n=151 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=140 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Time to First Improvement	31.00 days Interval 29.0 to 50.0	52.00 days Interval 49.0 to 71.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 weeks during the taper period

Population: Randomized participants who entered the taper period.

Treatment-emergent AEs were newly occurring AEs or a worsening of AEs during the taper period. A summary of serious AEs and other AEs during the treatment period (baseline through 10 weeks) is located in the Reported Adverse Events module.

Outcome measures

Measure	Duloxetine n=31 Participants 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=34 Participants A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).	Placebo n=114 Participants Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Tinnitus	2 participants	0 participants	0 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Vertigo	1 participants	0 participants	0 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Any Serious AE	0 participants	0 participants	0 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Dizziness	1 participants	1 participants	1 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Fatigue	0 participants	1 participants	2 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Hyperhidrosis	0 participants	0 participants	2 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Nausea	0 participants	1 participants	1 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Constipation	0 participants	0 participants	1 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Cystitis	0 participants	0 participants	1 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Headache	0 participants	0 participants	1 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Musculoskeletal Chest Pain	0 participants	1 participants	0 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Nightmare	0 participants	1 participants	0 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Oropharyngeal Pain	0 participants	1 participants	0 participants
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period Non-Serious AE, Pain	0 participants	0 participants	1 participants

Adverse Events

Duloxetine

Serious events: 3 serious events

Other events: 89 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Measure	Duloxetine n=151 participants at risk 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=140 participants at risk A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Cardiac disorders Angina pectoris	0.66% 1/151 • Number of events 1 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	0.00% 0/140 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Gastrointestinal disorders Large intestinal obstruction	0.66% 1/151 • Number of events 1 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	0.00% 0/140 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Vascular disorders Hypertensive crisis	0.66% 1/151 • Number of events 1 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	0.00% 0/140 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.

Other adverse events

Measure	Duloxetine n=151 participants at risk 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other). Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.	Placebo n=140 participants at risk A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Ear and labyrinth disorders Vertigo	3.3% 5/151 • Number of events 5 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	0.71% 1/140 • Number of events 1 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Gastrointestinal disorders Abdominal pain upper	4.0% 6/151 • Number of events 6 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	2.9% 4/140 • Number of events 4 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Gastrointestinal disorders Constipation	9.3% 14/151 • Number of events 14 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	3.6% 5/140 • Number of events 5 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Gastrointestinal disorders Diarrhoea	4.6% 7/151 • Number of events 8 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	3.6% 5/140 • Number of events 5 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Gastrointestinal disorders Dry mouth	7.3% 11/151 • Number of events 11 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	1.4% 2/140 • Number of events 2 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Gastrointestinal disorders Nausea	11.3% 17/151 • Number of events 18 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	6.4% 9/140 • Number of events 9 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Infections and infestations Nasopharyngitis	2.0% 3/151 • Number of events 3 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	7.1% 10/140 • Number of events 10 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Injury, poisoning and procedural complications Fall	4.0% 6/151 • Number of events 9 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	1.4% 2/140 • Number of events 2 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Metabolism and nutrition disorders Decreased appetite	4.0% 6/151 • Number of events 6 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	0.71% 1/140 • Number of events 1 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Musculoskeletal and connective tissue disorders Back pain	0.66% 1/151 • Number of events 1 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	4.3% 6/140 • Number of events 6 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Nervous system disorders Dizziness	7.9% 12/151 • Number of events 13 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	7.1% 10/140 • Number of events 11 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Nervous system disorders Headache	10.6% 16/151 • Number of events 18 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	6.4% 9/140 • Number of events 10 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Nervous system disorders Somnolence	6.0% 9/151 • Number of events 9 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	2.1% 3/140 • Number of events 3 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Psychiatric disorders Insomnia	1.3% 2/151 • Number of events 2 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	5.0% 7/140 • Number of events 7 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Skin and subcutaneous tissue disorders Hyperhidrosis	3.3% 5/151 • Number of events 5 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	0.00% 0/140 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
Skin and subcutaneous tissue disorders Pruritus	4.0% 6/151 • Number of events 6 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.	1.4% 2/140 • Number of events 2 • Baseline through 10 weeks. Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60